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Predictive Factors of the Response of Rectal Cancer to Neoadjuvant Radiochemotherapy
Department of Oncology and Surgical Sciences, Section of Surgery, University of Padova, Padova 35128, Italy
Istituto Oncologico Veneto-IRCCS, Padova 35128, Italy
Department of Oncology and Surgical Sciences, Section of Oncology, University of Padova, Padova 35128, Italy
* Author to whom correspondence should be addressed.
Received: 11 March 2011; in revised form: 8 April 2011 / Accepted: 11 April 2011 / Published: 26 April 2011
Abstract: Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), but the response is not uniform. Identification of patients with higher likelihood of responding to pRCT is clinically relevant, as patients with resistant tumors could be spared exposure to radiation or DNA-damaging drugs that are associated with adverse side effects. To highlight predictive biomarkers of response to pRCT, a systematic search of PubMed was conducted with a combination of the following terms: “rectal”, “predictive”, “radiochemotherapy”, “neoadjuvant”, “response” and “biomarkers”. Genetic polymorphisms in epithelial growth factor receptor (EGFR) and thymidylate synthase (TS) genes, the expression of several markers, such as EGFR, bcl-2/bax and cyclooxygenase (COX)-2, and circulating biomarkers, such as serum carcinoembryonic antigen (CEA) level, are promising as predictor markers, but need to be further evaluated. The majority of the studies did not support the predictive value of p53, while the values of Ki-67, TS and p21 is still controversial. Gene expression profiles of thousands of genes using microarrays, microRNA studies and the search for new circulating molecules, such as human telomerase reverse transcriptase mRNA and cell-free DNA, are providing interesting results that might lead to the identification of new useful biomarkers. Evaluation of biomarkers in larger, prospective trials are required to guide therapeutic strategies.
Keywords: rectal cancer; neoadjuvant therapy; biomarkers
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Spolverato, G.; Pucciarelli, S.; Bertorelle, R.; De Rossi, A.; Nitti, D. Predictive Factors of the Response of Rectal Cancer to Neoadjuvant Radiochemotherapy. Cancers 2011, 3, 2176-2194.
Spolverato G, Pucciarelli S, Bertorelle R, De Rossi A, Nitti D. Predictive Factors of the Response of Rectal Cancer to Neoadjuvant Radiochemotherapy. Cancers. 2011; 3(2):2176-2194.
Spolverato, Gaya; Pucciarelli, Salvatore; Bertorelle, Roberta; De Rossi, Anita; Nitti, Donato. 2011. "Predictive Factors of the Response of Rectal Cancer to Neoadjuvant Radiochemotherapy." Cancers 3, no. 2: 2176-2194.